tbuckley/cabot-search huggingface dataset:
Carbon Ion Radiotherapy in the Treatment of Hepatocellular Carcinoma
Authors: Hwa Kyung Byun, Changhwan Kim, Jinsil Seong
Journal: Clinical and Molecular Hepatology (2023)

Hepatocellular carcinoma (HCC) is a highly lethal cancer with limited treatment options and poor prognosis. Carbon ion radiotherapy (CIRT) has emerged as a promising treatment modality for HCC due to its unique physical and biological properties. CIRT uses carbon ions to target and destroy cancer cells with a high precision and efficacy. The Bragg Peak phenomenon allows precise dose delivery to the tumor while minimizing damage to healthy tissues. In addition, the high relative biological effectiveness of carbon ions can be shown against radioresistant and hypoxic tumor areas. CIRT also offers a shorter treatment schedule than conventional radiotherapy, which increases patient convenience and compliance. The clinical outcomes of CIRT for HCC have shown excellent local control rates with minimal side effects. Considering its physical and biological properties, CIRT may be a viable option for complex clinical scenarios such as patients with poor liver function, large tumors, re-irradiation cases, and tumors close to critical organs. Further research and larger studies are needed to establish definitive indications for CIRT and to compare its efficacy with that of other treatment modalities. Nevertheless, CIRT offers a potential breakthrough in HCC management, providing hope for improved therapeutic outcomes and reduced treatment-related toxicities.
Prospective study of e-cigarette use and respiratory symptoms in adolescents and young adults
Authors: Alayna P Tackett, Robert Urman, Jessica Barrington-Trimis, Feifei Liu, Hanna Hong, Mary Ann Pentz, Talat S Islam, Sandrah P Eckel, Meghan Rebuli, Adam Leventhal, Jonathan M Samet, Kiros Berhane, Rob McConnell
Journal: Thorax (2023)

Rationale Electronic cigarette (e-cigarette) aerosol contains volatile aldehydes, including flavourings and oxidant metals with known pulmonary toxicity. Objectives To evaluate the associations of e-cigarette use with symptoms of wheeze, bronchitic symptoms and shortness of breath (SOB) across 4 years of prospective data. Methods Participants completed questionnaires on respiratory symptoms and past 30-day e-cigarette, cigarette and cannabis use in 2014 (wave 1; N=2094; mean age 17.3 years, SD=0.6 years). Follow-up information was collected in 2015 (wave 2; n=1609), 2017 (wave 3; n=1502) and 2018 (wave 4; n=1637) using online surveys. Mixed-effects logistic regression models evaluated associations of e-cigarette use with respiratory symptoms. Measurements and main results Participants were mostly Hispanic white (51.8%) and evenly representative by sex (49.6% female; 50.4% male). Compared with never e-cigarette users, past 30-day e-cigarette users reported increased odds of wheeze (OR 1.81; 95% CI 1.28, 2.56), bronchitic symptoms (OR 2.06; 95% CI 1.58, 2.69) and SOB (OR 1.78; 95% CI 1.23, 2.57), adjusting for study wave, age, sex, race, lifetime asthma diagnosis and parental education. Effect estimates were attenuated (wheeze (OR 1.41; 95% CI 0.99, 2.01), bronchitic symptoms (OR 1.55; 95% CI 1.18, 2.05), SOB (OR 1.48; 95% CI 1.01, 2.18)), after adjusting additionally for current cigarette use, cannabis use and secondhand exposure to e-cigarettes/cigarettes/cannabis. Conclusions E-cigarette use in young adults was associated with respiratory symptoms, independent of combustible cannabis and cigarette exposures.
Adverse Impact of Cannabis on Human Health
Authors: Mark Chandy, Masataka Nishiga, Tzu-Tang Wei, Naomi M. Hamburg, Kari Nadeau, Joseph C. Wu
Journal: Annual Review of Medicine (2023)

Cannabis, the most commonly used recreational drug, is illicit in many areas of the world. With increasing decriminalization and legalization, cannabis use is increasing in the United States and other countries. The adverse effects of cannabis are unclear because its status as a Schedule 1 drug in the United States restricts research. Despite a paucity of data, cannabis is commonly perceived as a benign or even beneficial drug. However, recent studies show that cannabis has adverse cardiovascular and pulmonary effects and is linked with malignancy. Moreover, case reports have shown an association between cannabis use and neuropsychiatric disorders. With growing availability, cannabis misuse by minors has led to increasing incidences of overdose and toxicity. Though difficult to detect, cannabis intoxication may be linked to impaired driving and motor vehicle accidents. Overall, cannabis use is on the rise, and adverse effects are becoming apparent in clinical data sets.
Randomized Phase II Multicenter Trial of Abiraterone Acetate With or Without Cabazitaxel in the Treatment of Metastatic Castration-Resistant Prostate Cancer
Authors: Susan F. Slovin, Karen Knudsen, Susan Halabi, Renee de Leeuw, Ayesha Shafi, Praneet Kang, Steven Wolf, Bin Luo, Anuradha Gopalan, Tracy Curley, Mark Fleming, Ana Molina, Celina Fernandez, Kevin Kelly
Journal: Journal of Clinical Oncology (2023)

Improving clinical outcomes with novel drug combinations to treat metastatic castration-resistant prostate cancer (mCRPC) is challenging. Preclinical studies showed cabazitaxel had superior antitumor efficacy compared with docetaxel. Gene expression profiling revealed divergent effects of these taxanes in cycling cells. mCRPC are RB deficient rendering them hypersensitive to taxanes. These data suggested that upfront treatment with cabazitaxel with abiraterone may affect therapeutic response. We designed a phase II randomized noncomparative trial of abiraterone acetate/prednisone (AAP) or AAP and cabazitaxel (AAP + C) in men with mCRPC to address this hypothesis.This trial of 81 men with mCRPC determined the radiographic progression-free survival (rPFS), prostate-specific antigen (PSA) progression-free survival, overall objective response, and safety of AAP or AAP + C. Equally allocated patients received AAP followed by switching to cabazitaxel upon radiographic progression (arm 1) or upfront with AAP + C (arm 2). Patients were stratified into high-/low-risk groups by the Halabi nomogram. Real-time assessment of RB status and circulating tumor cell (CTC) analysis to correlate with clinical outcomes was exploratory.Both treatment arms were well-tolerated. Median rPFS in AAP was 6.4 months (95% CI, 3.8 to 10.6) and median overall survival (OS) 18.3 months (95% CI, 14.4 to 37.6), respectively. Fifty-six percent of patients showed ≥50% decline in PSA. Median rPFS in AAP + C was 14.8 months (95% CI, 10.6 to 16.4), and median OS 24.5 months (95% CI, 20.4 to 35.0). There was a ≥50% decline in PSA in 92.1% of men. Neither RB expression in pretherapy tumor biopsy, CTC, or tissue explants identified those who may benefit from AAP + C.AAP + C was safe with improved rPFS, OS duration, and a higher proportion of PSA declines. This suggests that AAP + C given earlier rather than sequentially may benefit some men. Further work is needed to identify this population.
CC16: A Treatable Trait in Asthma?
Authors: Chloe I. Bloom, Ian M. Adcock
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

A Treatable Trait in Asthma?The club cell secretory protein (CC16) gene, found on chromosome 11q12.3, is highly expressed in the airways and encodes the pneumoprotein CC16.This protein is so richly secreted by bronchiolar club cells and other epithelial cells that it is one of the most abundant proteins in respiratory secretions (1).CC16 is reported to have several protective functions, including antiinflammatory, immunomodulatory, and antioxidant effects (2).It has also been implicated as a biomarker for several lung states and conditions, including lung function decline, airway hyperresponsiveness, acute lung injury, cystic fibrosis, and chronic obstructive pulmonary disease (3-7).In asthma, depletion of circulating CC16 has been associated with both childhood and adult asthma, but only in cross-sectional studies (8, 9).Interestingly, low CC16 mRNA expression in bronchial epithelial cells was associated with asthma severity, as well as type 2 inflammation (10).Although showing potential as a novel biomarker for asthma, this still left many questions, including, Does CC16 provide more information than our traditional biomarkers of type 2 inflammation?and, Can CC16 predict the natural course of asthma?Up to one-third of children with symptoms at 7 years old will continue to experience them in adult life (11,12).Although some parameters, such as childhood obstructive spirometry and particular genetic factors, correlate with persistence into adult life, there are currently no applicable predictive models (11).In this issue of the Journal, Voraphani and colleagues (pp.758-769) sought to investigate the longitudinal relationship of circulating CC16 from childhood to adult life and its association with symptom persistence into adulthood (13).To undertake this task, they used three well-characterized, population-based birth cohorts, from the United States (TCRS [Tucson Children's Respiratory Study]), Sweden (BAMSE [Barn/children, Allergy, Milieu, Stockholm, Epidemiological survey]), and the United Kingdom (MAAS [Manchester Asthma and Allergy Study]).They measured circulating CC16 concentrations in 3,124 children and analyzed genotype data for the SNP rs3741240, the strongest protein quantitative trait locus for serum CC16.Reassuringly, circulating CC16 effects were consistent across the three cohorts, including the sex reversal effect of lower concentrations in boys during childhood but lower concentrations in women during adulthood.Circulating CC16 deficits, by 1 SD, were associated with a 20% increased odds of asthma, even after accounting for potential confounders such as sex, ethnicity, early-life respiratory illnesses, and atopy.Furthermore, there appeared to be a dose effect, as more frequent symptoms were more strongly associated with low CC16 (40% increased odds) than less frequent symptoms.Interestingly,
Integrative Oncology Care of Symptoms of Anxiety and Depression in Adults With Cancer: Society for Integrative Oncology–ASCO Guideline
Authors: Linda E. Carlson, Nofisat Ismaila, Elizabeth L. Addington, Gary N. Asher, Chloe Atreya, Lynda G. Balneaves, Joke Bradt, Nina Fuller-Shavel, Joseph Goodman, Caroline J. Hoffman, Alissa Huston, Ashwin Mehta, Channing J. Paller, Kimberly Richardson, Dugald Seely, Chelsea J. Siwik, Jennifer S. Temel, Julia H. Rowland
Journal: Journal of Clinical Oncology (2023)

To provide evidence-based recommendations to health care providers on integrative approaches to managing anxiety and depression symptoms in adults living with cancer.The Society for Integrative Oncology and ASCO convened an expert panel of integrative oncology, medical oncology, radiation oncology, surgical oncology, palliative oncology, social sciences, mind-body medicine, nursing, methodology, and patient advocacy representatives. The literature search included systematic reviews, meta-analyses, and randomized controlled trials published from 1990 through 2023. Outcomes of interest included anxiety or depression symptoms as measured by validated psychometric tools, and adverse events. Expert panel members used this evidence and informal consensus with the Guidelines into Decision Support methodology to develop evidence-based guideline recommendations.The literature search identified 110 relevant studies (30 systematic reviews and 80 randomized controlled trials) to inform the evidence base for this guideline.Recommendations were made for mindfulness-based interventions (MBIs), yoga, relaxation, music therapy, reflexology, and aromatherapy (using inhalation) for treating symptoms of anxiety during active treatment; and MBIs, yoga, acupuncture, tai chi and/or qigong, and reflexology for treating anxiety symptoms after cancer treatment. For depression symptoms, MBIs, yoga, music therapy, relaxation, and reflexology were recommended during treatment, and MBIs, yoga, and tai chi and/or qigong were recommended post-treatment.Issues of patient-health care provider communication, health disparities, comorbid medical conditions, cost implications, guideline implementation, provider training and credentialing, and quality assurance of natural health products are discussed. While several approaches such as MBIs and yoga appear effective, limitations of the evidence base including assessment of risk of bias, nonstandardization of therapies, lack of diversity in study samples, and lack of active control conditions as well as future research directions are discussed.Additional information is available at www.asco.org/survivorship-guidelines.
An Evaluation of the Asthma Impact of the June 2023 New York City Wildfire Air Pollution Episode
Authors: George Thurston, Wuyue Yu, David Luglio
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"An Evaluation of the Asthma Impact of the June 2023 New York City Wildfire Air Pollution Episode." American Journal of Respiratory and Critical Care Medicine, 208(8), pp. 898–900
A Multicenter, Single-Arm, Prospective Trial Assessing the Diagnostic Yield of Electromagnetic Bronchoscopic and Transthoracic Navigation for Peripheral Pulmonary Nodules
Authors: Jeffrey Thiboutot, Nicholas J. Pastis, Jason Akulian, Gerard A. Silvestri, Alexander Chen, Momen M. Wahidi, Christopher R. Gilbert, Cheng Ting Lin, Jenna Los, Eric Flenaugh, Roy Semaan, A. Cole Burks, Priya Sathyanarayan, Sam Wu, David Feller-Kopman, George Z. Cheng, Raed Alalawi, Najib M. Rahman, Fabien Maldonado, Hans J. Lee, Lonny Yarmus
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

Rationale: Strict adherence to procedural protocols and diagnostic definitions is critical to understand the efficacy of new technologies. Electromagnetic navigational bronchoscopy (ENB) for lung nodule biopsy has been used for decades without a solid understanding of its efficacy, but offers the opportunity for simultaneous tissue acquisition via electromagnetic navigational transthoracic biopsy (EMN-TTNA) and staging via endobronchial ultrasound (EBUS). Objective: To evaluate the diagnostic yield of EBUS, ENB, and EMN-TTNA during a single procedure using a strict a priori definition of diagnostic yield with central pathology adjudication. Methods: A prospective, single-arm trial was conducted at eight centers enrolling participants with pulmonary nodules (<3 cm; without computed tomography [CT]– and/or positron emission tomography–positive mediastinal lymph nodes) who underwent a staged procedure with same-day CT, EBUS, ENB, and EMN-TTNA. The procedure was staged such that, when a diagnosis had been achieved via rapid on-site pathologic evaluation, the procedure was ended and subsequent biopsy modalities were not attempted. A study finding was diagnostic if an independent pathology core laboratory confirmed malignancy or a definitive benign finding. The primary endpoint was the diagnostic yield of the combination of CT, EBUS, ENB, and EMN-TTNA. Measurements and Main Results: A total of 160 participants at 8 centers with a mean nodule size of 18 ± 6 mm were enrolled. The diagnostic yield of the combined procedure was 59% (94 of 160; 95% confidence interval [CI], 51–66%). Nodule regression was found on same-day CT in 2.5% of cases (4 of 160; 95% CI, 0.69–6.3%), and EBUS confirmed malignancy in 7.1% of cases (11 of 156; 95% CI, 3.6–12%). The yield of ENB alone was 49% (74 of 150; 95% CI, 41–58%), that of EMN-TTNA alone was 27% (8 of 30; 95% CI, 12–46%), and that of ENB plus EMN-TTNA was 53% (79 of 150; 95% CI, 44–61%). Complications included a pneumothorax rate of 10% and a 2% bleeding rate. When EMN-TTNA was performed, the pneumothorax rate was 30%. Conclusions: The diagnostic yield for ENB is 49%, which increases to 59% with the addition of same-day CT, EBUS, and EMN-TTNA, lower than in prior reports in the literature. The high complication rate and low diagnostic yield of EMN-TTNA does not support its routine use. Clinical trial registered with www.clinicaltrials.gov (NCT 03338049).
Associations between cardiorespiratory fitness in youth and the incidence of site-specific cancer in men: a cohort study with register linkage
Authors: Aron Onerup, Kirsten Mehlig, Agnes af Geijerstam, Elin Ekblom-Bak, Hans Georg Kuhn, Lauren Lissner, Maria Åberg, Mats Börjesson
Journal: British Journal of Sports Medicine (2023)

Objectives To assess the associations between cardiorespiratory fitness (CRF) in young men and the incidence of site-specific cancer. Methods A Swedish population-based cohort study with register linkage of men who underwent military conscription in 1968–2005 was undertaken. CRF was assessed by maximal aerobic workload cycle test at conscription. Cox regression models assessed linear associations and included CRF, age, year and site of conscription, body mass index and parental level of education. CRF was also categorised into low, moderate and high for facilitated interpretation and results comparing high and low CRF are reported. Results Primary analyses were performed in 1 078 000 men, of whom 84 117 subsequently developed cancer in at least one site during a mean follow-up of 33 years. Higher CRF was linearly associated with a lower hazard ratio (HR) of developing cancer in the head and neck (n=2738, HR 0.81, 95% CI 0.74 to 0.90), oesophagus (n=689, HR 0.61, 95% CI 0.50 to 0.74), stomach (n=902, HR 0.79, 95% CI 0.67 to 0.94), pancreas (n=1280, HR 0.88, 95% CI 0.76 to 1.01), liver (n=1111, HR 0.60, 95% CI 0.51 to 0.71), colon (n=3222, HR 0.82, 95% CI 0.75 to 0.90), rectum (n=2337, HR 0.95, 95% CI 0.85 to 1.05), kidney (n=1753, HR 0.80, 95% CI 0.70 to 0.90) and lung (n=1635, HR 0.58, 95% CI 0.51 to 0.66). However, higher CRF predicted a higher hazard of being diagnosed with prostate cancer (n=14 232, HR 1.07, 95% CI 1.03 to 1.12) and malignant skin cancer (n=23 064, HR 1.31, 95% CI 1.27 to 1.36). Conclusion We report a number of protective associations between higher CRF in healthy young men and the subsequent hazard of site-specific cancers. These results have implications for public health policymaking, strengthening the incentive to promote health through improving CRF in youth.
PB1989: STUDY ON THE RELATIONSHIP BETWEEN MDS AND ABNORMAL LIPID METABOLISM IN BONE MARROW MICROENVIRONMENT
Authors: Yuchun LI, Xiaodong Lyu
Journal: HemaSphere (2023)

Topic: 9. Myelodysplastic syndromes - Biology & Translational Research Background: Myelodysplastic Neoplasms (MDS) is a highly heterogeneous myeloid tumor derived from bone marrow. Bone marrow microenvironment is the environment for the occurrence and survival of MDS cells, in which bone marrow adipocytes (BMAs) are an important part, which can secrete a large number of adipocytokines to stimulate the occurrence and progression of MDS. In previous studies, our team found that about 80% of MDS was accompanied by gene mutations, but the mutated genes were highly heterogeneous and diverse, suggesting that gene mutations may be the result of deeper causes of MDS occurrence. To sum up, it is suggested that bone marrow adipocytokines may be closely related to the occurrence and progression of MDS, and the related mutations may be the adaptive changes of tumor cells stimulated by adipocytokines. Aims: To analyze the level of adipocytokines in bone marrow of MDS and to explore the relationship between adipocytokines and MDS subtypes, mutant genes and clonal heterogeneity. Methods: ELISA was used to detect the level of adipocytokines in the bone marrow of 64 MDS patients and 24 MDS-related secondary AML (sAML) patients, including CTRP1, leptin, adiponectin, adipsin, visfatin, and TNFa, IL-6, CCL2, SCF and CXCL12. High-throughput sequencing was used to detect 65 MDS-related genes in 70 patients, and the clone attributes were determined according to the variant allele frequency (VAF) values of the gene mutation. Results: The analysis of adipocytokines in bone marrow and subtypes of MDS showed that the level of visfatin increased gradually in MDS with no blasts, MDS with increased blasts and sAML (P=0.002). However, the level of SCF in sAML was significantly lower than that in MDS with increased blasts (P =0.015), and the level of CTRP1 was significantly higher (P=0.041). The results of gene mutation detection showed that mutated genes were detected in 45 patients (64%), including 16 cases (36%) with 1 mutation, 15 cases (33%) with 2 mutations, and 10 cases (22%) with 3 mutations, 4 cases of 4 mutations (9%). The correlation analysis between adipocytokines and gene mutations showed that the incidence of MDS mutant gene increased significantly with the decrease of leptin and CXCL12 expression levels（P=0.03, P=0.009).According to the information of gene mutation, 27 (60％) patients with 1 clone, 14 (31%) patients with 2 clones, and 4 cases (9%) with 3 clones. The clone heterogeneity of MDS mutant gene was significantly enhanced when the expression levels of leptin and CXCL12 were decreased (P=0.008, P=0.022). Summary/Conclusion: The level of adipocytokines in bone marrow is closely related to the differentiation of MDS cells, the occurrence of gene mutation and its clonal heterogeneity, which is helpful to further clarify the influencing factors and mechanism of the occurrence and progression of MDS. Keywords: MDS, Bone marrow microenvironment, Lipid metabolism, Gene mutation
Extensive Cardiac Function Analyses Using Contemporary Echocardiography in Childhood Cancer Survivors
Authors: Remy Merkx, Jan M. Leerink, E. (Lieke) A.M. Feijen, Esmée C. de Baat, Louise Bellersen, Dorine Bresters, Elvira C. van Dalen, Eline van Dulmen-den Broeder, Margriet van der Heiden-van der Loo, Marry M. van den Heuvel-Eibrink, Judith L. Kok, Marloes Louwerens, Angela H.E.M. Maas, Sebastian J.C.M.M. Neggers, Cécile M. Ronckers, Jop C. Teepen, Arco J. Teske, Wim J.E. Tissing, Andrica C.H. de Vries, Gert Weijers, Chris L. de Korte, Jacqueline Loonen, Annelies M.C. Mavinkurve-Groothuis, Helena J.H. van der Pal, Leontien C.M. Kremer, Wouter E.M. Kok, Livia Kapusta
Journal: JACC CardioOncology (2023)

Childhood cancer survivors (CCS) are at risk for cardiotoxicity.We sought to assess how cardiac dysfunction measurements in CCS overlap and are differentially influenced by risk factors.This cross-sectional Dutch Childhood Cancer Survivor Study evaluated echocardiograms of 1,397 ≥5-year CCS and 277 siblings. Of CCS, n = 1,254 received cardiotoxic (anthracyclines/mitoxantrone/radiotherapy involving the heart region [RTheart]) and n = 143 received potentially cardiotoxic (cyclophosphamide, ifosfamide, or vincristine) therapy. We assessed demographic, treatment-related, and traditional cardiovascular risk factors for cardiac dysfunction using multivariable logistic regression.CCS were a median of 26.7 years after diagnosis; 49% were women. Abnormal left ventricular ejection fraction (LVEF) (defined as <52% in men, <54% in women) occurred most commonly in CCS treated with anthracyclines and RTheart combined (38%). Age/sex-specific abnormal global longitudinal strain (GLS) occurred most commonly in CCS treated with RTheart, either with (41%) or without (38%) anthracyclines. Of CCS with normal LVEF, 20.2% showed abnormal GLS. Diastolic dysfunction grade ≥II was rare. Abnormal LVEF was mainly associated with female sex, anthracycline dose, and only in women, RTheart dose. Abnormal GLS was associated with female sex, RTheart dose, diastolic blood pressure, and only in women, anthracycline dose. Cyclophosphamide, ifosfamide, and vincristine were not associated with LVEF or GLS. Compared with siblings, CCS showed higher risk of abnormal LVEF (OR: 2.9; 95% CI: 1.4-6.6) and GLS (OR: 2.1; 95% CI: 1.2-3.7), independent of (potentially) cardiotoxic treatment-related and cardiovascular risk factors.Abnormal LVEF and GLS constitute complementary measures of systolic dysfunction among long-term CCS. Their diagnostic value may differ according to cardiotoxic exposures. Also, CCS have residual, unexplained risk of cardiac dysfunction. (Early Detection of Cardiac Dysfunction in Childhood Cancer Survivors, a DCOG LATER study; NTR7481).